The potential of gene delivery for the treatment of traumatic brain injury.
AAV
Gene delivery
Neuroimmunology
TBI
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
28 Jul 2024
28 Jul 2024
Historique:
received:
01
04
2024
accepted:
17
06
2024
medline:
29
7
2024
pubmed:
29
7
2024
entrez:
28
7
2024
Statut:
epublish
Résumé
Therapeutics for traumatic brains injuries constitute a global unmet medical need. Despite the advances in neurocritical care, which have dramatically improved the survival rate for the ~ 70 million patients annually, few treatments have been developed to counter the long-term neuroinflammatory processes and accompanying cognitive impairments, frequent among patients. This review looks at gene delivery as a potential therapeutic development avenue for traumatic brain injury. We discuss the capacity of gene delivery to function in traumatic brain injury, by producing beneficial biologics within the brain. Gene delivery modalities, promising vectors and key delivery routes are discussed, along with the pathways that biological cargos could target to improve long-term outcomes for patients. Coupling blood-brain barrier crossing with sustained local production, gene delivery has the potential to convert proteins with useful biological properties, but poor pharmacodynamics, into effective therapeutics. Finally, we review the limitations and health economics of traumatic brain injury, and whether future gene delivery approaches will be viable for patients and health care systems.
Identifiants
pubmed: 39069631
doi: 10.1186/s12974-024-03156-x
pii: 10.1186/s12974-024-03156-x
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
183Subventions
Organisme : Medical Research Council
ID : MR/X029166/1
Pays : United Kingdom
Informations de copyright
© 2024. The Author(s).
Références
Dewan MC, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018;130:1080–97.
pubmed: 29701556
doi: 10.3171/2017.10.JNS17352
Maas AIR, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16:987–1048.
pubmed: 29122524
doi: 10.1016/S1474-4422(17)30371-X
Steyerberg EW, et al. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study. Lancet Neurol. 2019;18:923–34.
pubmed: 31526754
doi: 10.1016/S1474-4422(19)30232-7
Hubbard WB, et al. Clinically relevant mitochondrial-targeted therapy improves chronic outcomes after traumatic brain injury. Brain. 2021;144:3788–807.
pubmed: 34972207
pmcid: 8719838
doi: 10.1093/brain/awab341
Tyurin VA, et al. Oxidative stress following traumatic brain injury in rats: quantitation of biomarkers and detection of free radical intermediates. J Neurochem. 2000;75:2178–89.
pubmed: 11032908
doi: 10.1046/j.1471-4159.2000.0752178.x
George KK, Heithoff BP, Shandra O, Robel S. Mild traumatic Brain Injury/Concussion initiates an atypical astrocyte response caused by blood-brain barrier dysfunction. J Neurotrauma. 2022;39:211–26.
pubmed: 34806422
pmcid: 8785769
doi: 10.1089/neu.2021.0204
Kochanek PM, et al. Cerebral blood flow at one year after controlled cortical impact in rats: assessment by magnetic resonance imaging. J Neurotrauma. 2002;19:1029–37.
pubmed: 12482116
doi: 10.1089/089771502760341947
Bolte AC, Lukens JR. Neuroimmune cleanup crews in brain injury. Trends Immunol. 2021;42:480–94.
pubmed: 33941486
pmcid: 8165004
doi: 10.1016/j.it.2021.04.003
Mackay DF, et al. Neurodegenerative disease mortality among former Professional Soccer players. N Engl J Med. 2019;381:1801–8.
pubmed: 31633894
pmcid: 8747032
doi: 10.1056/NEJMoa1908483
Mez J, et al. Clinicopathological evaluation of Chronic Traumatic Encephalopathy in players of American Football. JAMA. 2017;318:360–70.
pubmed: 28742910
pmcid: 5807097
doi: 10.1001/jama.2017.8334
Abner EL, et al. Self-reported head injury and risk of late-life impairment and AD pathology in an AD center cohort. Dement Geriatr Cogn Disord. 2014;37:294–306.
pubmed: 24401791
doi: 10.1159/000355478
Ahmed S, et al. Traumatic brain Injury and Neuropsychiatric complications. Indian J Psychol Med. 2017;39:114–21.
pubmed: 28515545
pmcid: 5385737
doi: 10.4103/0253-7176.203129
Goldman SM, et al. Head injury and Parkinson’s disease risk in twins. Ann Neurol. 2006;60:65–72.
pubmed: 16718702
doi: 10.1002/ana.20882
Liu G et al. Head Injury and Amyotrophic lateral sclerosis: a Meta-analysis. Neuroepidemiology, 1–9 (2021).
Turner RC, et al. Repetitive traumatic brain injury and development of chronic traumatic encephalopathy: a potential role for biomarkers in diagnosis, prognosis, and treatment? Front Neurol. 2012;3:186.
pubmed: 23335911
Das M, Mohapatra S, Mohapatra SS. New perspectives on central and peripheral immune responses to acute traumatic brain injury. J Neuroinflammation. 2012;9:236.
pubmed: 23061919
pmcid: 3526406
doi: 10.1186/1742-2094-9-236
Loane DJ, Kumar A, Stoica BA, Cabatbat R, Faden AI. Progressive neurodegeneration after experimental brain trauma: association with chronic microglial activation. J Neuropathol Exp Neurol. 2014;73:14–29.
pubmed: 24335533
doi: 10.1097/NEN.0000000000000021
Pischiutta F, et al. Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury. Exp Neurol. 2018;300:167–78.
pubmed: 29126888
doi: 10.1016/j.expneurol.2017.11.003
Witcher KG, et al. Traumatic brain Injury causes chronic cortical inflammation and neuronal dysfunction mediated by Microglia. J Neurosci. 2021;41:1597–616.
pubmed: 33452227
pmcid: 7896020
doi: 10.1523/JNEUROSCI.2469-20.2020
Nagamoto-Combs K, McNeal DW, Morecraft RJ, Combs CK. Prolonged microgliosis in the rhesus monkey central nervous system after traumatic brain injury. J Neurotrauma. 2007;24:1719–42.
pubmed: 18001202
doi: 10.1089/neu.2007.0377
Johnson VE, et al. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain. 2013;136:28–42.
pubmed: 23365092
pmcid: 3562078
doi: 10.1093/brain/aws322
Gentleman SM, et al. Long-term intracerebral inflammatory response after traumatic brain injury. Forensic Sci Int. 2004;146:97–104.
pubmed: 15542269
doi: 10.1016/j.forsciint.2004.06.027
Rodriguez-Paez AC, Brunschwig JP, Bramlett HM. Light and electron microscopic assessment of progressive atrophy following moderate traumatic brain injury in the rat. Acta Neuropathol. 2005;109:603–16.
pubmed: 15877231
doi: 10.1007/s00401-005-1010-z
Smith C, et al. The neuroinflammatory response in humans after traumatic brain injury. Neuropathol Appl Neurobiol. 2013;39:654–66.
pubmed: 23231074
doi: 10.1111/nan.12008
Reddy DS, Abeygunaratne HN. Experimental and Clinical Biomarkers for Progressive Evaluation of Neuropathology and therapeutic interventions for Acute and Chronic Neurological disorders. Int J Mol Sci 23 (2022).
Guilfoyle MR, et al. Matrix Metalloproteinase expression in Contusional Traumatic Brain Injury: a paired Microdialysis Study. J Neurotrauma. 2015;32:1553–9.
pubmed: 25858502
pmcid: 4593877
doi: 10.1089/neu.2014.3764
Shigemori Y, Katayama Y, Mori T, Maeda T, Kawamata T. Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats. Acta Neurochir Suppl. 2006;96:130–3.
pubmed: 16671440
doi: 10.1007/3-211-30714-1_29
Mi L, et al. Neutrophil extracellular traps aggravate neuronal endoplasmic reticulum stress and apoptosis via TLR9 after traumatic brain injury. Cell Death Dis. 2023;14:374.
pubmed: 37365190
pmcid: 10293297
doi: 10.1038/s41419-023-05898-7
Yshii L, et al. Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation. Nat Immunol. 2022;23:878–91.
pubmed: 35618831
pmcid: 9174055
doi: 10.1038/s41590-022-01208-z
Daglas M, et al. Activated CD8(+) T cells cause long-term neurological impairment after traumatic brain Injury in mice. Cell Rep. 2019;29:1178–e11911176.
pubmed: 31665632
doi: 10.1016/j.celrep.2019.09.046
Izzy S, et al. Time-dependent changes in Microglia Transcriptional Networks following traumatic Brain Injury. Front Cell Neurosci. 2019;13:307.
pubmed: 31440141
pmcid: 6694299
doi: 10.3389/fncel.2019.00307
Kumar A, Alvarez-Croda DM, Stoica BA, Faden AI, Loane DJ. Microglial/Macrophage polarization Dynamics following traumatic Brain Injury. J Neurotrauma. 2016;33:1732–50.
pubmed: 26486881
pmcid: 5065034
doi: 10.1089/neu.2015.4268
Madathil SK, et al. Early microglial activation following closed-Head Concussive Injury is dominated by pro-inflammatory M-1 type. Front Neurol. 2018;9:964.
pubmed: 30498469
pmcid: 6249371
doi: 10.3389/fneur.2018.00964
Turtzo LC, et al. Macrophagic and microglial responses after focal traumatic brain injury in the female rat. J Neuroinflammation. 2014;11:82.
pubmed: 24761998
pmcid: 4022366
doi: 10.1186/1742-2094-11-82
Liddelow SA, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541:481–7.
pubmed: 28099414
pmcid: 5404890
doi: 10.1038/nature21029
Clark DPQ, et al. Inflammation in traumatic Brain Injury: roles for toxic A1 astrocytes and microglial-astrocytic crosstalk. Neurochem Res. 2019;44:1410–24.
pubmed: 30661228
doi: 10.1007/s11064-019-02721-8
Toutonji A, Mandava M, Guglietta S, Tomlinson S. Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study. Acta Neuropathol Commun. 2021;9:126.
pubmed: 34281628
pmcid: 8287781
doi: 10.1186/s40478-021-01226-2
Early AN, Gorman AA, Van Eldik LJ, Bachstetter AD, Morganti JM. Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice. J Neuroinflammation. 2020;17:115.
pubmed: 32290848
pmcid: 7158022
doi: 10.1186/s12974-020-01800-w
Todd BP, et al. Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response. J Neuroinflammation. 2021;18:151.
pubmed: 34225752
pmcid: 8259035
doi: 10.1186/s12974-021-02197-w
Brennan FH, et al. Microglia coordinate cellular interactions during spinal cord repair in mice. Nat Commun. 2022;13:4096.
pubmed: 35835751
pmcid: 9283484
doi: 10.1038/s41467-022-31797-0
Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV. Essential protective roles of reactive astrocytes in traumatic brain injury. Brain. 2006;129:2761–72.
pubmed: 16825202
doi: 10.1093/brain/awl165
Henry RJ, et al. Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain Injury reduces neurodegeneration and neurological deficits. J Neurosci. 2020;40:2960–74.
pubmed: 32094203
pmcid: 7117897
doi: 10.1523/JNEUROSCI.2402-19.2020
Willis EF, et al. Repopulating Microglia promote Brain Repair in an IL-6-Dependent manner. Cell. 2020;180:833–e846816.
pubmed: 32142677
doi: 10.1016/j.cell.2020.02.013
Hutchinson PJ, et al. Trial of Decompressive Craniectomy for traumatic intracranial hypertension. N Engl J Med. 2016;375:1119–30.
pubmed: 27602507
doi: 10.1056/NEJMoa1605215
Timofeev I, et al. Ventriculostomy for control of raised ICP in acute traumatic brain injury. Acta Neurochir Suppl. 2008;102:99–104.
pubmed: 19388297
doi: 10.1007/978-3-211-85578-2_20
Achar A, Myers R, Ghosh C. Drug Delivery challenges in Brain disorders across the blood-brain barrier: novel methods and future considerations for Improved Therapy. Biomedicines 9 (2021).
Bulaklak K, Gersbach CA. The once and future gene therapy. Nat Commun. 2020;11:5820.
pubmed: 33199717
pmcid: 7670458
doi: 10.1038/s41467-020-19505-2
Ramamoorth M, Narvekar A. Non viral vectors in gene therapy- an overview. J Clin Diagn Res. 2015;9:GE01–06.
pubmed: 25738007
pmcid: 4347098
Sung YK, Kim SW. Recent advances in the development of gene delivery systems. Biomater Res. 2019;23:8.
pubmed: 30915230
pmcid: 6417261
doi: 10.1186/s40824-019-0156-z
Hayward A. Origin of the retroviruses: when, where, and how? Curr Opin Virol. 2017;25:23–7.
pubmed: 28672160
pmcid: 5962544
doi: 10.1016/j.coviro.2017.06.006
Lewis PF, Emerman M. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol. 1994;68:510–6.
pubmed: 8254763
pmcid: 236313
doi: 10.1128/jvi.68.1.510-516.1994
Bayer M, et al. A large U3 deletion causes increased in vivo expression from a nonintegrating lentiviral vector. Mol Ther. 2008;16:1968–76.
pubmed: 18797449
doi: 10.1038/mt.2008.199
Yanez-Munoz RJ, et al. Effective gene therapy with nonintegrating lentiviral vectors. Nat Med. 2006;12:348–53.
pubmed: 16491086
doi: 10.1038/nm1365
Marcocci ME, et al. Herpes simplex Virus-1 in the brain: the Dark side of a sneaky infection. Trends Microbiol. 2020;28:808–20.
pubmed: 32386801
doi: 10.1016/j.tim.2020.03.003
Todo T, Ino Y, Ohtsu H, Shibahara J, Tanaka M. A phase I/II study of triple-mutated oncolytic herpes virus G47∆ in patients with progressive glioblastoma. Nat Commun. 2022;13:4119.
pubmed: 35864115
pmcid: 9304402
doi: 10.1038/s41467-022-31262-y
Friedman GK, et al. Oncolytic HSV-1 G207 immunovirotherapy for Pediatric High-Grade Gliomas. N Engl J Med. 2021;384:1613–22.
pubmed: 33838625
pmcid: 8284840
doi: 10.1056/NEJMoa2024947
Kardani K, Sanchez Gil J, Rabkin SD. Oncolytic herpes simplex viruses for the treatment of glioma and targeting glioblastoma stem-like cells. Front Cell Infect Microbiol. 2023;13:1206111.
pubmed: 37325516
pmcid: 10264819
doi: 10.3389/fcimb.2023.1206111
Harrow S, et al. HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival. Gene Ther. 2004;11:1648–58.
pubmed: 15334111
doi: 10.1038/sj.gt.3302289
Jarnagin WR, et al. Neoadjuvant treatment of hepatic malignancy: an oncolytic herpes simplex virus expressing IL-12 effectively treats the parent tumor and protects against recurrence-after resection. Cancer Gene Ther. 2003;10:215–23.
pubmed: 12637943
doi: 10.1038/sj.cgt.7700558
Popescu M, Van Belleghem JD, Khosravi A, Bollyky PL. Bacteriophages and the Immune System. Annu Rev Virol. 2021;8:415–35.
pubmed: 34014761
doi: 10.1146/annurev-virology-091919-074551
Uyttebroek S, et al. Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review. Lancet Infect Dis. 2022;22:e208–20.
pubmed: 35248167
doi: 10.1016/S1473-3099(21)00612-5
Majerova P et al. Novel blood-brain barrier shuttle peptides discovered through the Phage Display Method. Molecules 25 (2020).
Podlacha M et al. Interactions of bacteriophages with animal and human organisms-Safety issues in the light of phage therapy. Int J Mol Sci 22 (2021).
Przystal JM et al. Efficacy of systemic temozolomide-activated phage-targeted gene therapy in human glioblastoma. EMBO Mol Med 11 (2019).
Martinez BI, et al. Uncovering temporospatial sensitive TBI targeting strategies via in vivo phage display. Sci Adv. 2022;8:eabo5047.
pubmed: 35867794
pmcid: 9307250
doi: 10.1126/sciadv.abo5047
Syyam A, et al. Adenovirus vector system: construction, history and therapeutic applications. Biotechniques. 2022;73:297–305.
pubmed: 36475496
doi: 10.2144/btn-2022-0051
Watanabe M, Nishikawaji Y, Kawakami H, Kosai KI. Adenovirus Biology, recombinant adenovirus, and adenovirus usage in Gene Therapy. Viruses 13 (2021).
Ji N, et al. Adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of recurrent high-grade glioma. Oncotarget. 2016;7:4369–78.
pubmed: 26716896
doi: 10.18632/oncotarget.6737
Yoshida J, Mizuno M, Nakahara N, Colosi P. Antitumor effect of an adeno-associated virus vector containing the human interferon-beta gene on experimental intracranial human glioma. Jpn J Cancer Res. 2002;93:223–8.
pubmed: 11856487
pmcid: 5926956
doi: 10.1111/j.1349-7006.2002.tb01262.x
Barton KN, et al. Second-generation replication-competent oncolytic adenovirus armed with improved suicide genes and ADP gene demonstrates greater efficacy without increased toxicity. Mol Ther. 2006;13:347–56.
pubmed: 16290236
doi: 10.1016/j.ymthe.2005.10.005
Issa SS, Shaimardanova AA, Solovyeva VV, Rizvanov AA. Various AAV Serotypes and Their Applications in Gene Therapy: An Overview. Cells 12 (2023).
Srivastava A. In vivo tissue-tropism of adeno-associated viral vectors. Curr Opin Virol. 2016;21:75–80.
pubmed: 27596608
pmcid: 5138125
doi: 10.1016/j.coviro.2016.08.003
Wang D, Tai PWL, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov. 2019;18:358–78.
pubmed: 30710128
pmcid: 6927556
doi: 10.1038/s41573-019-0012-9
Ghauri MS, Ou L. AAV Engineering for improving tropism to the Central Nervous System. Biology (Basel) 12 (2023).
Hordeaux J, et al. The Neurotropic properties of AAV-PHP.B are limited to C57BL/6J mice. Mol Ther. 2018;26:664–8.
pubmed: 29428298
pmcid: 5911151
doi: 10.1016/j.ymthe.2018.01.018
Goertsen D, et al. AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset. Nat Neurosci. 2022;25:106–15.
pubmed: 34887588
doi: 10.1038/s41593-021-00969-4
Wu Z, Yang H, Colosi P. Effect of genome size on AAV vector packaging. Mol Ther. 2010;18:80–6.
pubmed: 19904234
doi: 10.1038/mt.2009.255
Whiteley LO. An overview of nonclinical and clinical liver toxicity Associated with AAV Gene Therapy. Toxicol Pathol, 1926233231201408 (2023).
Kuzmin DA, et al. The clinical landscape for AAV gene therapies. Nat Rev Drug Discov. 2021;20:173–4.
pubmed: 33495615
doi: 10.1038/d41573-021-00017-7
Macdonald J, Marx J, Buning H. Capsid-Engineering for Central Nervous System-Directed Gene Therapy with Adeno-Associated Virus vectors. Hum Gene Ther. 2021;32:1096–119.
pubmed: 34662226
doi: 10.1089/hum.2021.169
Foust KD, et al. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009;27:59–65.
pubmed: 19098898
doi: 10.1038/nbt.1515
Mendell JR, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377:1713–22.
pubmed: 29091557
doi: 10.1056/NEJMoa1706198
Zhang H, et al. Several rAAV vectors efficiently cross the blood-brain barrier and transduce neurons and astrocytes in the neonatal mouse central nervous system. Mol Ther. 2011;19:1440–8.
pubmed: 21610699
pmcid: 3149178
doi: 10.1038/mt.2011.98
Kugler S. Tissue-specific promoters in the CNS. Methods Mol Biol. 2016;1382:81–91.
pubmed: 26611580
doi: 10.1007/978-1-4939-3271-9_6
Nieuwenhuis B, et al. Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: comparison of four promoters. Gene Ther. 2021;28:56–74.
pubmed: 32576975
doi: 10.1038/s41434-020-0169-1
Leone P, et al. Long-term follow-up after gene therapy for canavan disease. Sci Transl Med. 2012;4:165ra163.
pubmed: 23253610
pmcid: 3794457
doi: 10.1126/scitranslmed.3003454
Iliff JJ, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012;4:147ra111.
pubmed: 22896675
pmcid: 3551275
doi: 10.1126/scitranslmed.3003748
Mestre H, Mori Y, Nedergaard M. The Brain’s Glymphatic System: current controversies. Trends Neurosci. 2020;43:458–66.
pubmed: 32423764
pmcid: 7331945
doi: 10.1016/j.tins.2020.04.003
Hinderer C, et al. Widespread gene transfer in the central nervous system of cynomolgus macaques following delivery of AAV9 into the cisterna magna. Mol Ther Methods Clin Dev. 2014;1:14051.
pubmed: 26052519
pmcid: 4448732
doi: 10.1038/mtm.2014.51
Hordeaux J, et al. Toxicology Study of Intra-cisterna magna Adeno-Associated Virus 9 expressing Iduronate-2-Sulfatase in Rhesus Macaques. Mol Ther Methods Clin Dev. 2018;10:68–78.
pubmed: 30073178
pmcid: 6070702
doi: 10.1016/j.omtm.2018.06.004
Bailey RM, Rozenberg A, Gray SJ. Comparison of high-dose intracisterna magna and lumbar puncture intrathecal delivery of AAV9 in mice to treat neuropathies. Brain Res. 2020;1739:146832.
pubmed: 32289279
pmcid: 7997047
doi: 10.1016/j.brainres.2020.146832
Lochhead JJ, Thorne RG. Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev. 2012;64:614–28.
pubmed: 22119441
doi: 10.1016/j.addr.2011.11.002
Belur LR, et al. Intranasal Adeno-Associated Virus mediated Gene Delivery and expression of human iduronidase in the Central Nervous System: a Noninvasive and Effective Approach for Prevention of neurologic disease in mucopolysaccharidosis type I. Hum Gene Ther. 2017;28:576–87.
pubmed: 28462595
pmcid: 5549804
doi: 10.1089/hum.2017.187
Wolf DA, et al. Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration. Mol Genet Metab. 2012;106:131–4.
pubmed: 22420937
doi: 10.1016/j.ymgme.2012.02.006
Ye D, et al. Incisionless targeted adeno-associated viral vector delivery to the brain by focused ultrasound-mediated intranasal administration. EBioMedicine. 2022;84:104277.
pubmed: 36152518
pmcid: 9508404
doi: 10.1016/j.ebiom.2022.104277
Ng SY, Lee AYW. Traumatic brain injuries: pathophysiology and potential therapeutic targets. Front Cell Neurosci. 2019;13:528.
pubmed: 31827423
pmcid: 6890857
doi: 10.3389/fncel.2019.00528
Needham EJ, et al. The immunological response to traumatic brain injury. J Neuroimmunol. 2019;332:112–25.
pubmed: 31005712
doi: 10.1016/j.jneuroim.2019.04.005
Simon DW, et al. The far-reaching scope of neuroinflammation after traumatic brain injury. Nat Rev Neurol. 2017;13:572.
pubmed: 28776601
doi: 10.1038/nrneurol.2017.116
Helmy A, et al. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial. J Cereb Blood Flow Metab. 2014;34:845–51.
pubmed: 24569690
pmcid: 4013762
doi: 10.1038/jcbfm.2014.23
Shemer A, et al. Interleukin-10 prevents pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge. Immunity. 2020;53:1033–e10491037.
pubmed: 33049219
doi: 10.1016/j.immuni.2020.09.018
Kiyota T, et al. AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP + PS1 mice. Gene Ther. 2012;19:724–33.
pubmed: 21918553
doi: 10.1038/gt.2011.126
Choi BR, Johnson KR, Maric D, McGavern DB. Monocyte-derived IL-6 programs microglia to rebuild damaged brain vasculature. Nat Immunol. 2023;24:1110–23.
pubmed: 37248420
doi: 10.1038/s41590-023-01521-1
Kiyota T, et al. AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. Mol Ther. 2009;17:803–9.
pubmed: 19277012
pmcid: 2709991
doi: 10.1038/mt.2009.44
Liston A, Pasciuto E, Fitzgerald DC, Yshii L. Brain regulatory T cells. Nat Rev Immunol. 2024;24:326–37.
pubmed: 38040953
doi: 10.1038/s41577-023-00960-z
Deng S, et al. Recruitment of regulatory T cells with rCCL17 promotes M2 microglia/macrophage polarization through TGFbeta/TGFbetaR/Smad2/3 pathway in a mouse model of intracerebral hemorrhage. Exp Neurol. 2023;367:114451.
pubmed: 37257716
doi: 10.1016/j.expneurol.2023.114451
Grewer C, et al. Glutamate forward and reverse transport: from molecular mechanism to transporter-mediated release after ischemia. IUBMB Life. 2008;60:609–19.
pubmed: 18543277
pmcid: 2632779
doi: 10.1002/iub.98
Rossi DJ, Oshima T, Attwell D. Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature. 2000;403:316–21.
pubmed: 10659851
doi: 10.1038/35002090
Shen Z, et al. Glutamate excitotoxicity: potential therapeutic target for ischemic stroke. Biomed Pharmacother. 2022;151:113125.
pubmed: 35609367
doi: 10.1016/j.biopha.2022.113125
Green JL, Santos D, W.F., Fontana ACK. Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: opportunities for novel therapeutics development. Biochem Pharmacol. 2021;193:114786.
pubmed: 34571003
pmcid: 8605998
doi: 10.1016/j.bcp.2021.114786
Krasil’nikova I, et al. Insulin protects cortical neurons against Glutamate Excitotoxicity. Front Neurosci. 2019;13:1027.
pubmed: 31611766
pmcid: 6769071
doi: 10.3389/fnins.2019.01027
Jiao SS, et al. Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease. Transl Psychiatry. 2016;6:e907.
pubmed: 27701410
pmcid: 5315549
doi: 10.1038/tp.2016.186
Fesharaki-Zadeh A. Oxidative stress in traumatic brain Injury. Int J Mol Sci 23 (2022).
Forman HJ, Zhang H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 2021;20:689–709.
pubmed: 34194012
pmcid: 8243062
doi: 10.1038/s41573-021-00233-1
Ottaviano FG, Handy DE, Loscalzo J. Redox regulation in the extracellular environment. Circ J. 2008;72:1–16.
pubmed: 18159092
doi: 10.1253/circj.72.1
Bartus K, et al. Large-scale chondroitin sulfate proteoglycan digestion with chondroitinase gene therapy leads to reduced pathology and modulates macrophage phenotype following spinal cord contusion injury. J Neurosci. 2014;34:4822–36.
pubmed: 24695702
pmcid: 3972714
doi: 10.1523/JNEUROSCI.4369-13.2014
Didangelos A, Iberl M, Vinsland E, Bartus K, Bradbury EJ. Regulation of IL-10 by chondroitinase ABC promotes a distinct immune response following spinal cord injury. J Neurosci. 2014;34:16424–32.
pubmed: 25471580
pmcid: 4252552
doi: 10.1523/JNEUROSCI.2927-14.2014
Dyck S, et al. Perturbing chondroitin sulfate proteoglycan signaling through LAR and PTPsigma receptors promotes a beneficial inflammatory response following spinal cord injury. J Neuroinflammation. 2018;15:90.
pubmed: 29558941
pmcid: 5861616
doi: 10.1186/s12974-018-1128-2
Bradbury EJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 2002;416:636–40.
pubmed: 11948352
doi: 10.1038/416636a
Finan JD, Cho FS, Kernie SG, Morrison B 3. Intracerebroventricular administration of chondroitinase ABC reduces acute edema after traumatic brain injury in mice. BMC Res Notes. 2016;9:160.
Harris NG, Nogueira MS, Verley DR, Sutton RL. Chondroitinase enhances cortical map plasticity and increases functionally active sprouting axons after brain injury. J Neurotrauma. 2013;30:1257–69.
pubmed: 23517225
pmcid: 3713450
doi: 10.1089/neu.2012.2737
Harris NG, Mironova YA, Hovda DA, Sutton RL. Chondroitinase ABC enhances pericontusion axonal sprouting but does not confer robust improvements in behavioral recovery. J Neurotrauma. 2010;27:1971–82.
pubmed: 20809786
pmcid: 2978059
doi: 10.1089/neu.2010.1470
Conniot J, Talebian S, Simoes S, Ferreira L, Conde J. Revisiting gene delivery to the brain: silencing and editing. Biomater Sci. 2021;9:1065–87.
pubmed: 33315025
doi: 10.1039/D0BM01278E
van Dijck J, et al. In-hospital costs after severe traumatic brain injury: a systematic review and quality assessment. PLoS ONE. 2019;14:e0216743.
pubmed: 31071199
pmcid: 6508680
doi: 10.1371/journal.pone.0216743
Wood RL, McCrea JD, Wood LM, Merriman RN. Clinical and cost effectiveness of post-acute neurobehavioural rehabilitation. Brain Inj. 1999;13:69–88.
pubmed: 10079953
doi: 10.1080/026990599121746
Ridley S, Morris S. Cost effectiveness of adult intensive care in the UK. Anaesthesia. 2007;62:547–54.
pubmed: 17506731
doi: 10.1111/j.1365-2044.2007.04997.x
Slade A, Tennant A, Chamberlain MA. A randomised controlled trial to determine the effect of intensity of therapy upon length of stay in a neurological rehabilitation setting. J Rehabil Med. 2002;34:260–6.
pubmed: 12440799
doi: 10.1080/165019702760390347
Williams J et al. Cost-effectiveness analysis of tranexamic acid for the treatment of traumatic brain injury, based on the results of the CRASH-3 randomised trial: a decision modelling approach. BMJ Glob Health 5 (2020).
Grieve R, et al. An evaluation of the clinical and cost-effectiveness of alternative care locations for critically ill adult patients with acute traumatic brain injury. Br J Neurosurg. 2016;30:388–96.
pubmed: 27188663
doi: 10.3109/02688697.2016.1161166
Faul M, Wald MM, Rutland-Brown W, Sullivent EE, Sattin RW. Using a cost-benefit analysis to estimate outcomes of a clinical treatment guideline: testing theBrain Trauma Foundation guidelines for the treatment of severe traumatic brain injury. J Trauma. 2007;63:1271–8.
pubmed: 18212649
Gustavsson A, et al. Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21:718–79.
pubmed: 21924589
doi: 10.1016/j.euroneuro.2011.08.008
Norup A, Kruse M, Soendergaard PL, Rasmussen KW, Biering-Sorensen F. Socioeconomic consequences of traumatic Brain Injury: a Danish Nationwide Register-based study. J Neurotrauma. 2020;37:2694–702.
pubmed: 32808586
doi: 10.1089/neu.2020.7064
Hesdorffer DC, Rauch SL, Tamminga CA. Long-term psychiatric outcomes following traumatic brain injury: a review of the literature. J Head Trauma Rehabil. 2009;24:452–9.
pubmed: 19940678
doi: 10.1097/HTR.0b013e3181c133fd
Dillahunt-Aspillaga C, et al. Traumatic brain injury: unmet support needs of caregivers and families in Florida. PLoS ONE. 2013;8:e82896.
pubmed: 24358236
pmcid: 3866264
doi: 10.1371/journal.pone.0082896